This is a broad program of study of the biochemistry of the thyroid gland and normal and abnormal aspects of thyroid hormone economy. Among the major aspects considered are: 1. The intermediary metabolism of the thyroid and its relation to hormonogenesis. Here, especial attention will be directed at the relationship betwen glandular metabolism and the mechanism of thyroglobulin hydrolysis and hormone release. 2. Studies of the acute and chronic response to iodine administration. Emphasis here will be placed on studies of the mechanism whereby iodine exerts the variety of its inhibitory effects on thyroid function. 3. Studies of the regulation of TSH secretion. Special attention will be directed to the study of neonatal thyrotoxicosis induced by either thyroid hormone or TRH administration. Additional studies will continue concerning factors that affect TRH-responsiveness in man. 4. Studies of the transport and metabolism of thyroid hormones. Particular emphasis will be placed on the peripheral conversion of thyroxine to triiodothyronine, including factors that influence this process, its alteration in various disease states, and its role in determining the degree of thyroid hormone action. Studies of the physiological role of tetraiodothyroacetic acid will also be conducted. 5. Studies of the tissue mechanisms for thyroid hormone degradation. Human leukocytes and issue macrophages will continue to be used as model systems for hormonal deiodination. 6. Studies of the physiopathology of thyroid diseases. Among the disorders and their particular aspects to be studied are: The natural history of Graves' disease; the pathogenesis of non-toxic goiter.